Procedural Sedation

Anatomy and Physiology

The most severe complication of procedural sedation and analgesia is respiratory failure due to airway obstruction or hypoventilation. A thorough understanding of airway anatomy, its variations, and any history of airway anomalies is essential. The Mallampati score is the most commonly used scale for airway anatomy assessment.[9] Evaluation should consider anatomic features that may impact airway management, such as dysmorphic or asymmetrical facial features, significant malnutrition or cachexia with sunken cheeks and missing teeth, neck injuries, and facial trauma, including lacerations through the cheek or unstable bony injuries. Limited neck extension and a mouth opening of less than 4 to 5 cm, which restrict access, require further assessment. Obesity can also hinder adequate ventilation and oxygenation, even in the absence of other risk factors.

Indications

Procedural sedation and analgesia are indicated for procedures that may cause significant pain and anxiety. The required sedation level depends on the anticipated pain, anxiety, and the need for the patient to remain still during the procedure. For instance, an orthopedic procedure requiring joint reduction and muscle relaxation demands deeper sedation than a less uncomfortable procedure. Decision-making must also consider the patient's hemodynamic stability.

A thorough review of the patient's history, including chronic diseases such as cardiovascular or respiratory conditions, drug history, and allergies, is essential for evaluating the risk of adverse events during the intended procedure and while the patient is sedated. The most commonly used system for clinical assessment is the ASA Physical Status (Class) scoring, as follows:

• ASA class 1: A normal, healthy patient. Examples include a nonsmoker and an individual with no or minimal alcohol use.

• ASA class 2: A patient with mild systemic disease without significant functional limitations. Examples include a current smoker, social alcohol drinker, pregnancy, body mass index (BMI) between 30 and 40, controlled preeclampsia without severe features, well-controlled diabetes mellitus or hypertension, and mild lung disease.

• ASA class 3: A patient with severe systemic disease and substantial functional limitation with 1 or more moderate-to-severe diseases. Examples include poorly controlled diabetes mellitus or hypertension, chronic obstructive pulmonary disease, morbid obesity (BMI ≥40), active hepatitis, alcohol dependence or abuse, an implanted pacemaker, moderate reduction of ejection fraction, end-stage renal disease undergoing regularly scheduled dialysis, or a history (>3 months) of myocardial infarction, cerebrovascular accident, transient ischemic attack, or coronary artery disease with stents.

• ASA class 4: A patient with severe systemic disease that is a constant threat to life. Examples include recent (<3 months) myocardial infarction, cerebrovascular accident, transient ischemic attack, or coronary artery disease with stents; ongoing cardiac ischemia or severe valve dysfunction; severe reduction of ejection fraction; shock; sepsis; preeclampsia with severe features complicated by adverse events, such as HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets); disseminated intravascular coagulation; acute renal disease; or end-stage renal disease not undergoing regularly scheduled dialysis.

• ASA class 5: A moribund patient who is not expected to survive without surgery. Examples include a ruptured abdominal or thoracic aneurysm, uterine rupture, massive trauma, intracranial bleed with mass effect, ischemic bowel in the presence of significant cardiac pathology, or multiple organ or system dysfunction.

• ASA class 6: A patient declared brain dead whose organs are being removed for donor purposes.[10]

Adding E to the physical status classification indicates emergency surgery, defined as a procedure necessary to prevent a life-threatening condition or the loss of a body part if delayed.

Contraindications

Procedural sedation and analgesia have no absolute contraindications but may be inappropriate in certain situations, as outlined below:

• Operator skillset and training: Procedural sedation and analgesia should not be performed if the healthcare provider lacks the skills to secure an unstable airway, including intubation and cricothyrotomy.
• Lack of appropriate monitoring and resuscitation equipment: Procedural sedation and analgesia should not proceed if necessary equipment is unavailable.
• Patient needs: If the procedure is more extensive than a brief painful intervention, such as surgery, general anesthesia in an operating room may be more appropriate.
• Patient conditions: Patients with a high ASA risk score may require treatment by a qualified anesthetist. Of particular concern are individuals classified as unstable ASA class II or IV and above unless immediate intervention is necessary, such as for ventricular tachycardia conversion.
• Medication allergies or adverse reactions: Procedural sedation and analgesia should be avoided in patients with known allergies or adverse reactions to the medications used in sedation.

Most institutions follow a policy requiring a preprocedural fasting period of 6 hours for solid food and 2 hours for clear liquids. However, current literature indicates that aspiration during elective procedures is rare.[11][12] According to ASA practice guidelines for moderate Procedural sedation and analgesia, sedation should not be delayed solely based on fasting time in urgent or emergent situations where complete gastric emptying is not feasible.

Equipment

Before initiating procedural sedation and analgesia, the healthcare provider should confirm the availability and functionality of the following equipment:

• Intravenous access
• Medications and equipment for cardiac resuscitation, including a defibrillator
• Oxygen administration equipment, ranging from a nasal cannula to a nonrebreather mask
• Suction device
• Airway equipment, including a bag-valve mask, laryngeal mask airway, bougie, direct or video-assisted laryngoscopy with appropriate blades, and appropriately sized oral airways and endotracheal tubes; surgical and needle airway equipment should also be available
• Reversal agents, including naloxone and flumazenil
• Monitoring equipment, including a cardiac monitor, blood pressure cuff, pulse oximeter, and end-tidal carbon dioxide monitor

Personnel

Ideally, two healthcare providers should be present during the procedure—one to perform the intended procedure and the other to manage sedation, monitor the patient, and coordinate the team. However, having two healthcare providers is not feasible in many situations, particularly for unplanned procedures. In these cases, a nurse or another qualified individual should continuously monitor the patient while the healthcare provider performs the procedure, with support from an emergency department clinician and staff for coordination.

The healthcare provider administering procedural sedation and analgesia must be able to:

• Implement appropriate patient screening and selection.
• Exhibit advanced airway management skills.
• Understand and administer sedation and analgesic medications, including reversal agents.
• Monitor airway patency and recognize signs of airway obstruction.
• Assess ventilatory adequacy by evaluating chest wall motion, pulse oximetry, and capnography.
• Evaluate cardiovascular stability through cardiac rhythm monitoring, blood pressure assessment, and physical examination.
• Manage all potential complications.

Preparation

Before initiating the procedure, a comprehensive medical evaluation should be conducted to minimize risks during and after sedation. A standardized checklist enhances process adherence and ensures safety. However, its use has not been shown to reduce sedation-related adverse events significantly.[13] The checklist should include the following:

• Consent obtained from the patient or primary caregiver
• Physical status evaluation based on the ASA classification system
• A comprehensive health evaluation, including age, weight, health conditions requiring additional considerations, current medications, allergies, and relevant personal or family medical history
• Verification of the patient's identity and the procedure to be performed
• Availability of required medications, including reversal drugs
• The patient's fasting status
• Functionality of monitoring devices
• Assessment for airway difficulties or anomalies using the Mallampati score
• Individual confirmation of team members' roles and preparations

Technique or Treatment

Medications

The ideal agent for procedural sedation and analgesia should provide sedative, analgesic, and amnestic effects while ensuring a rapid onset and short duration of action. These properties support safe, efficient recovery and timely discharge. Procedural sedation and analgesia commonly involve combining a short-acting benzodiazepine, such as midazolam, with an opioid, such as fentanyl. Midazolam provides sedative, amnestic, and anxiolytic effects but lacks analgesic properties, which fentanyl supplements. However, several other medications may be used alone or in combination.[14] Short-acting agents such as propofol or etomidate are suitable for sedation in healthy patients. When intravenous access is unavailable, intranasal midazolam and intranasal fentanyl offer alternative options.

For patients at risk of hypotension due to cardiac disease, dehydration, or other conditions, etomidate or ketamine may be considered. Ketamine and dexmedetomidine do not cause respiratory depression and may be appropriate for patients with airway complications. In patients with obesity, dosing should be based on ideal or adjusted body weight to prevent oversedation. Older patients require lower doses to minimize adverse events.

Midazolam: Midazolam provides sedation, anxiolysis, and amnesia. Flumazenil serves as midazolam's antidote. However, caution is necessary as flumazenil may have a shorter duration of action than midazolam, leading to resedation. In older patients, careful monitoring is essential to prevent benzodiazepine-induced neurocognitive alterations.[15][16]

When administered intravenously, the initial dose ranges from 0.5 to 2.5 mg, with repeat dosing every 2 to 5 minutes as required. In healthy young adults, total doses exceeding 5 mg are rarely required, whereas debilitated and older patients typically need less than 3.5 mg. When given intranasally, the dose is 0.1 mg/kg, with a maximum single dose of 10 mg, administered 15 to 20 minutes before the procedure. The dose should be divided equally between both nostrils. Midazolam can cause a burning sensation in the nose, which may be reduced by using an atomizer for delivery.

Midazolam takes effect within 1 to 5 minutes when administered intravenously and within 10 minutes when administered intranasally. The peak effect occurs within 5 to 10 minutes and can last up to 60 minutes when given intravenously, whereas the nasal route provides effects lasting 20 to 25 minutes.

Fentanyl: Fentanyl is a synthetic opioid metabolized by the liver. This agent's high lipophilicity allows rapid redistribution to muscle and fat. Adverse effects include peripheral edema, low blood pressure, slow heart rate, confusion, and breathing suppression. Rapid intravenous administration can cause chest wall rigidity.[17]

When administered intravenously, the dose ranges from 0.5 to 1 mcg/kg every 2 to 3 minutes until the desired sedation and pain relief are achieved. When administered intranasally, the dose is 2 to 5 mcg/kg. Fentanyl takes effect within 1 to 2 minutes when administered intravenously, with effects lasting 30 to 60 minutes.

Ketamine

Ketamine provides sedation, amnesia, and analgesia with a lower risk of respiratory depression. This agent is administered intravenously at an initial dose of 1 to 2 mg/kg, with additional doses of 0.5 to 1 mg/kg every 5 to 10 minutes if required. When administered intramuscularly, the typical dose is 5 mg/kg, with repeat doses of 2 to 5 mg/kg if sedation is inadequate. Intravenous administration has an onset time of fewer than 30 seconds, whereas intramuscular administration takes approximately 3 to 4 minutes. The duration of action ranges from 5 to 10 minutes when administered intravenously and 10 to 25 minutes when administered intramuscularly.

Adverse effects include emergence reactions such as hallucinations, delirium, and vivid dreams. Ketamine can also increase heart rate and blood pressure due to sympathetic stimulation, leading to higher myocardial oxygen demand.[18] A rare but transient risk of laryngospasm exists. Coadministration of a benzodiazepine, such as midazolam or lorazepam, at the time of the final ketamine dose, may help reduce emergence reactions and sympathomimetic effects, particularly in children. Ketamine should be avoided in individuals predisposed to psychotic behavior.

As an emetogenic agent, ketamine can cause vomiting, though pretreatment with ondansetron or concurrent administration with propofol can reduce this risk. Ketamine does not increase intracranial pressure and is considered safe for use in patients with traumatic brain injury.[19] Other potential adverse effects include diplopia, nystagmus, and increased intraocular pressure.

Propofol: Propofol is administered intravenously at an initial dose of 0.5 to 1 mg/kg, with additional doses of 0.25 to 0.5 mg/kg every 2 to 3 minutes until the desired level of sedation is achieved. Onset occurs within 15 to 30 seconds, and its duration of action ranges from 3 to 10 minutes, depending on the dose. Propofol does not provide analgesia and is associated with significant adverse effects, including bradycardia, hypotension, and hypertriglyceridemia, which can lead to pancreatitis. Prolonged high-dose administration can result in propofol-related infusion syndrome, a rare but potentially fatal condition characterized by bradycardia, asystole, heart failure, metabolic acidosis, rhabdomyolysis, hypertriglyceridemia, and acute kidney injury.[20]

Ketamine with propofol: Combining ketamine with propofol (ketofol) can mitigate some of the adverse effects of each agent. This combination reduces ketamine-induced vomiting and emergence reactions while counteracting the hypotensive effects of propofol. Ketofol also provides effective pain control with early recovery. A standard mixture consists of 100 mg of ketamine in 10 mL and 100 mg of propofol in 10 mL. The initial ketofol dose is 0.375 to 0.5 mg/kg, with half of the initial dose repeated as needed to achieve adequate sedation and analgesia.[21]

Etomidate: Etomidate provides sedation but does not have analgesic properties, necessitating the administration of opioids before the procedure. This drug has minimal effects on cardiopulmonary function, making it a preferred choice in hemodynamically unstable patients. However, adverse effects include myoclonus, adrenal suppression, and nystagmus.[22] The recommended intravenous dose is 0.1 to 0.2 mg/kg, followed by 0.05 mg/kg every 3 to 5 minutes as required.[23] Onset occurs within 30 seconds to 1 minute, with a duration of action lasting 2 to 5 minutes. The duration may be prolonged in older adults and individuals with impaired renal function.

Dexmedetomidine: Dexmedetomidine provides sedation, analgesia, and anxiolysis without causing respiratory depression. However, achieving the desired level of sedation often requires the use of additional medications. The recommended intravenous dose is 1 mcg/kg, followed by a continuous infusion at 0.2 mcg/kg/h. Onset occurs within 3 to 5 minutes, with peak effects observed between 15 and 30 minutes.[24][25]

Methohexital: Methohexital, a barbiturate, is contraindicated in individuals with acute intermittent porphyria. Adverse reactions include bronchospasm, circulatory depression, headache, and pain at the injection site. Transient hypotension may occur due to vasodilation, which may be managed by administering intravenous fluids or having the patient sit up gradually. The recommended intravenous dose is 0.75 to 1 mg/kg, with a repeat dose of 0.5 mg/kg administered every 2 to 5 minutes as required. Onset occurs within 15 to 30 seconds, and the duration of action ranges from 5 to 15 minutes.[26]

Nitrous oxide: Nitrous oxide is a general central nervous system depressant that may exert mild analgesic effects through partial opioid receptor activity. This gas provides sedation, anxiolysis, mild analgesia, and amnesia, with a rapid onset and fast recovery.

Nitrous oxide is commonly used for procedural sedation and analgesia in dentistry, especially for pediatric patients.[27] The procedure typically begins with 100% oxygen, followed by a gradual reduction in oxygen while incrementally increasing the concentration of nitrous oxide. A flow rate of 5 to 6 L/min is generally well tolerated.

Although therapeutic levels vary among individuals, the concentration of nitrous oxide should not routinely exceed 50%.[28] The use of nitrous oxide is contraindicated in individuals experiencing severe emotional disturbances or drug-related dependencies, entering the first trimester of pregnancy, or undergoing treatment with bleomycin sulfate. Additional contraindications include a recent tympanic membrane graft and methylenetetrahydrofolate reductase deficiency.[29]

The recommended inhalational dose is 30% to 50% nitrous oxide with oxygen. The onset of action is within 2 to 5 minutes.

Reversal Agents

Reversal agents counteract the effects of specific sedatives or analgesics, restoring normal physiological function when excessive sedation or respiratory depression occurs. Two commonly used agents include naloxone for opioid reversal and flumazenil for benzodiazepine reversal.

Naloxone: Naloxone is administered intravenously at doses ranging from 0.05 to 2.0 mg, with repeat doses administered every 2 to 3 minutes as required, often in escalating amounts. The onset of action occurs in less than 2 minutes, with a duration lasting between 30 minutes and 2 hours, depending on the route of administration. Naloxone is essential for reversing opioid-induced respiratory depression, but its short half-life necessitates repeat dosing when reversing the effects of long-acting opioids.[30]

Flumazenil: Flumazenil is administered intravenously at an initial dose of 0.2 mg over 2 minutes, with additional doses of 0.2 mg administered at 1-minute intervals, up to a maximum total dose of 1 mg. Onset occurs within 1 to 2 minutes, with a duration of action lasting 45 to 60 minutes. Although flumazenil effectively reverses benzodiazepine sedation, its use in chronic benzodiazepine users is discouraged due to the risk of seizure induction.

Complications

Each medication used in procedural sedation and analgesia carries potential adverse effects. The objective is to select the most appropriate agent for the patient and the intended procedure. The clinician should know the risks and benefits associated with the procedure and planned sedation. The ideal approach involves sedating the patient for the shortest duration necessary to perform the procedure safely.

The most commonly reported complications are hypoxia, followed by vomiting and hypotension. Serious adverse events such as aspiration and laryngospasm requiring medical intervention are rare.[31] The incidence of agitation and vomiting is higher with ketamine, though concomitant use of propofol can reduce these effects. Apnea and hypoxia occur more frequently with benzodiazepines. The healthcare provider must be able to recognize signs of airway compromise and perform advanced airway management if necessary.

Clinical Significance

Procedural sedation and analgesia are effective methods that help patients tolerate short, painful procedures when performed correctly. The procedure must take place in a safe and controlled environment, with the healthcare provider prepared to manage any adverse events related to sedation.

Healthcare providers must anticipate complications such as vomiting, laryngospasm, hypotension, and cardiorespiratory depression and be ready to intervene as required. Close attention must be given to respiratory depression, which may be mitigated through continuous monitoring, particularly with end-tidal carbon dioxide, and by maintaining a low threshold for providing respiratory support, especially with bag-valve-mask ventilation. For hypotension, establishing intravenous access is essential to facilitate blood pressure support with intravenous fluids. When performed outside the operating room by skilled healthcare providers, such as intensivists, the risk of adverse outcomes is lower.[32]

Enhancing Healthcare Team Outcomes

Procedural sedation and analgesia highlight the importance of an interprofessional team approach in medicine. Ideally, two to three clinicians should be present—one to perform the procedure and others to administer sedation and monitor the patient. In resource-limited settings and many emergency departments, a trained nurse can monitor the patient, whereas the clinician performs the procedure.[33]

The operating clinician must be prepared to abandon the procedure if necessary to support the patient and manage adverse events. In these situations, a nurse or another trained staff member must provide continuous patient monitoring. Before the procedure begins, the team should confirm the availability of all resuscitative equipment and reversal agents. Clear interprofessional communication is essential for patient safety and optimal outcomes.

Nursing, Allied Health, and Interprofessional Team Interventions

Nurses are integral team members in procedural sedation, responsible for patient assessment based on nursing standards, managing the procedural environment, and ensuring proper monitoring. Ongoing training is essential for administering sedation medications and monitoring patients effectively. Professional societies should support nurses in practicing to the full extent of their licensure. Advocacy should focus on removing non-evidence-based restrictions on nursing practice to improve patient care and strengthen team collaboration.

Nursing, Allied Health, and Interprofessional Team Monitoring

Nurses must remain aware of errors caused by monitoring equipment interference. For example, inflating a blood pressure cuff can artificially lower oxygen saturation readings due to arterial compression. In addition, nurses should feel empowered to alert the clinician and the team to any observed adverse events.